The Big Bend of Florida, United States, is an informally named geographic region of North Florida where the Florida Panhandle transitions to the Florida Peninsula south and east of Tallahassee (the area's principal city). The region is known for its vast woodlands and marshlands and its low population density relative to much of the state. The area is home to the largest single spring in the United States, the Alapaha Rise, and the longest surveyed underwater cave in the United States, the 32-mile (51 km) Wakulla-Leon Sinks cave system.

The related Big Bend Coast region includes the marshy coast without barrier islands that extends along the Gulf of Mexico from the Ocklockonee River to Anclote Key. Florida's Nature Coast region is included in the Big Bend Coast.

The Big Bend region is located at the northern end of Apalachee Bay along the broad arc of land where the predominantly east–west coastline of the Florida Panhandle connects to the predominantly north–south geography of the Florida Peninsula. It stretches eastward from the Forgotten Coast past the delta of the Suwannee River, with some definitions extending the southwestern end as far as the edge of the Tampa Bay area. Inland areas are often covered with woodlands and marshes around the southward- and southwestward-trending rivers draining towards the Gulf of Mexico. The Big Bend region includes the area between the Apalachicola and Suwannee Rivers historically called Middle Florida. North Florida's portion of the Red Hills Region is located within the Big Bend region. The Big Bend Coast either contains or is coterminous with the Nature Coast.

Coastal areas such as the Woodville Karst Plain exhibit drowned karst topography covered with salt marshes and feature numerous freshwater springs and oyster reefs. Sinkholes, subterranean rivers, and underwater caves (such as the connected Wakulla Cave and Leon Sinks system) are common. The area has little or no sand or mud. No barrier islands exist between the Ocklockonee River and Anclote Key, and the karst topography of the area has produced an irregular, frequently exposed, bedrock surface.

Due to the width of the adjacent continental shelf (over 150 kilometers (93 mi)), low gradient slope of the coast (1:5000), and shelter from the usual wind direction of storms, the Big Bend Coast is generally subject to low wave energy, but it is subject to storm surges.

The region is traversed by numerous rivers, such as the Suwannee, Crystal, Santa Fe, Withlacoochee, Alapaha, and St. Marks Rivers. A number of these rivers have subterranean stretches, vanishing into the ground before reappearing hundreds or thousands of feet away. In addition to Tallahassee, other significant cities and towns in the region include Apalachicola, St. Marks, Carrabelle, Perry, Steinhatchee, and Cedar Key.

The Big Bend region is known for its springs. The area's karst topography is conducive to spring formation, and many of the resulting springs are protected by the state, including several designated as Outstanding Florida Springs.

The largest single spring in the United States, the Alapaha Rise, is located in the region near the confluence of the Suwannee River and Alapaha River. Other area springs include Wakulla Springs, St. Marks Spring, Wacissa Springs, Aucilla Spring, Madison Blue Springs, Ichetucknee Springs, Suwannee Springs, Hart Springs, Ginnie Springs, Fanning Springs, Manatee Springs, Otter Springs, Troy Spring, Rainbow Springs, Homosassa Springs, and Weeki Wachee Springs.